Lumacaftor (VX-809)

製品コードS1565 バッチS156505

印刷

化学情報

Chemical Structure Synonyms VRT 826809 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C24H18F2N2O5
分子量 452.41 CAS No. 936727-05-8
Solubility (25°C)* 体外 DMSO 90 mg/mL (198.93 mM)
Ethanol 13 mg/mL (28.73 mM)
Water Insoluble
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Lumacaftor (VX-809, VRT 826809) acts to correct CFTR mutations common in cystic fibrosis by increasing mutant CFTR (F508del-CFTR) maturation,EC50 of 0.1 μM in fisher rat thyroid cells. Phase 3.
in vitro

Lumacaftor (VX-809) acts at the level of the ER to allow a fraction of the F508del-CFTR to adopt a properly folded form, to exit the ER and mobilize to the cell surface for normal functioning. In Fischer rat thyroid (FRT) cells expressing F508del-CFTR, this compound treatment significantly improves F508del-CFTR maturation by 7.1 fold with an EC50 of 0.1 μM, and enhances F508del-CFTR-mediated chloride transport by approximately 5 fold with EC50 of 0.5 μM, while VRT-768 has higher EC50 values of 7.9 μM and 16 μM, respectively. In HEK-293 cells expressing F508del-CFTR, it (3 μM) treatment increases F508del-CFTR exit from the ER by 6 fold, reaching levels comparable to 34% of CFTR. In primary human bronchial epithelial (HBE) cells with F508del-CFTR mutation, the compound increases CFTR maturation and enhances chloride secretion with EC50 of 350 nM and 81 nM, respectively, more efficacious than Corr-4a and VRT-325. F508del-CFTR corrected by it exhibits single-channel open probability of 0.39 similar to normal CFTR of 0.40. Unlike VX-770, this compound is not a CFTR potentiator, as acute addition of it has no effect on F508del-CFTR function. In contrast to VRT-325 and Corr-4a, it does not improve the processing of the normal or mutant forms of hERG or P-gp, as well as other disease-causing mislocalized proteins, including α1-antitrypsin Z mutant (E342K-α1-AT) or N370S-β-glucosidase, suggesting that it is specific for CFTR. It in combination with VRT-325 or Corr-4a has additive effect on CFTR-mediated chloride transport in cultured F508del-HBE. [1]
in vivo

Lumacaftor (VX-809; VRT 826809) is a CFTR modulator that corrects the folding and trafficking of CFTR protein.
特徴 Higher specificity and efficacy relative to other CFTR defect drugs.

プロトコル(参考用のみ)

キナーゼアッセイ F508del-CFTR maturation
Lumacaftor (VX-809) is used to treat FRT cells stably expressing F508del-CFTR at increasing concentrations for 48 hours. After incubation, cells are harvested in ice-cold D-PBS solution (without calcium and magnesium) and pelleted at 1,000 × g at 4 °C. Cell pellets are lysed in 1% Nonidet P-40, 0.5% sodium deoxycholate, 200 mM NaCl, 10 mM Tris, pH 7.8, and 1 mM EDTA plus protease inhibitor mixture (1:250) for 30 minutes on ice. Lysates are spun for 10 minutes at 10,000 × g at 4 °C to pellet nuclei and insoluble material. Approximately 12 μg total protein is heated in Laemmli buffer with 5% β-mercaptoethanol at 37 °C for 5 minutes and loaded onto a 3% to 8% Tris-acetate gel. The gel is transferred to nitrocellulose and processed for Western blotting by using monoclonal CFTR antibody or polyclonal to GAPDH. Blots are developed by enhanced chemiluminescence. Quantification of the relative amounts of bands C and GAPDH is performed by using NIH ImageJ analysis of scanned films.
細胞アッセイ 細胞株 FRT (CFTR or F508del-CFTR), HEK-293 (CFTT or F508del-CFTR) , and HBE cells
濃度 Dissolved in DMSO, final concentrations ~0.1 mM
反応時間 24 or 48 hours
実験の流れ

Cells are exposed to various concentrations of Lumacaftor (VX-809) for 24 or 48 hours. Ussing chamber techniques are used to record the transepithelial current (IT) resulting from CFTR-mediated chloride transport. The single-channel activity of CFTR is measured by using excised inside-out membrane patch recordings. Immunoblot techniques using the monoclonal CFTR antibody are used to measure CFTR maturation in FRT, HEK-293, or HBE cells expressing CFTR or F508del-CFTR.
動物実験 動物モデル Male Sprague– Dawley rats
投薬量 1 mg/kg
投与方法 p.o.

参考

  • https://pubmed.ncbi.nlm.nih.gov/21976485/

カスタマーフィードバック

Data from [J Biol Chem, 2012, 287, 43630-8]

, , Xuehong Liu of Oregon Health & Science University

,

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

ACE-tRNAs are a platform technology for suppressing nonsense mutations that cause cystic fibrosis [ Nucleic Acids Res, 2025, 53(13)gkaf675] PubMed: 40650978
In silico, in vitro and ex vivo characterization of cystic fibrosis transmembrane conductance regulator pathogenic variants localized in the fourth intracellular loop and their rescue by modulators [ Br J Pharmacol, 2025, 10.1111/bph.70176] PubMed: 40831301
Global functional genomics reveals GRK5 as a cystic fibrosis therapeutic target synergistic with current modulators [ iScience, 2025, 28(3):111942] PubMed: 40040803
Human Induced Lung Organoids: A Promising Tool for Cystic Fibrosis Drug Screening [ Int J Mol Sci, 2025, 26(2)437] PubMed: 39859153
Nasal cells as a bronchial cell surrogate for pre-clinical assessment of drug response in cystic fibrosis [ Front Pharmacol, 2025, 16:1651122] PubMed: 40978488
Inhibitors of the ubiquitin‑proteasome system rescue cellular levels and ion transport function of pathogenic pendrin (SLC26A4) protein variants [ Int J Mol Med, 2025, 55(5)69] PubMed: 40052591
The Inhibition of the Membrane-Bound Transcription Factor Site-1 Protease (MBTP1) Alleviates the p.Phe508del-Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Defects in Cystic Fibrosis Cells [ Cells, 2024, 13(2)185] PubMed: 38247876
Comprehensive Assessment of CFTR Modulators' Therapeutic Efficiency for N1303K Variant [ Int J Mol Sci, 2024, 25(5)2770] PubMed: 38474016
Estimation of Chloride Channel Residual Function and Assessment of Targeted Drugs Efficiency in the Presence of a Complex Allele [L467F;F508del] in the CFTR Gene [ Int J Mol Sci, 2024, 25(19)10424] PubMed: 39408749
The F508del-CFTR trafficking correctors elexacaftor and tezacaftor are CFTR-independent Ca2+-mobilizing agonists normalizing abnormal Ca2+ levels in human airway epithelial cells [ Respir Res, 2024, 25(1):436] PubMed: 39702307

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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